Patterns of ethanol intake in male rats with partial dopamine transporter deficiency.

Mesolimbic dopamine signaling plays a major role in alcohol and substance use disorders as well as comorbidities such as anxiety and depression. Growing evidence suggests that alcohol drinking is modulated by the function of the dopamine transporter (DAT), which tightly regulates extracellular dopamine concentrations. Adult male rats on a Wistar Han background (DAT+/+) and rats with a partial DAT deletion (DAT+/-) were used in this study. First, using fast-scan cyclic voltammetry in brain slices containing the nucleus accumbens core from ethanol-naïve subjects, we measured greater evoked dopamine concentrations and slower dopamine reuptake in DAT+/- rats, consistent with increased dopamine signaling. Next, we measured ethanol drinking using the intermittent access two-bottle choice paradigm (20% v/v ethanol vs. water) across 5 weeks. DAT+/- rats voluntarily consumed less ethanol during its initial availability (the first 30 min), especially after longer periods of deprivation. In addition, DAT+/- males consumed less ethanol that was adulterated with the bitter tastant quinine. These findings suggest that partial DAT blockade and concomitant increase in brain dopamine levels has potential to reduce drinking and ameliorate alcohol use disorder (AUD).

Effects of temperature variation on suicide in five U.S. counties, 1991-2001.

Effects of weather variables on suicide are well-documented, but there is still little consistency among the results of most studies. Nevertheless, most studies show a peak in suicides during the spring season, and this is often attributed to increased temperatures. The purpose of this study is to test the relationship between monthly temperature and monthly suicide, independent of months or seasons, for five counties located across the United States. Harmonic analysis shows that four of the five counties display some seasonal components in the suicide data. However, simple linear regression shows no correlation between suicide and temperature, and discriminant analysis shows that monthly departure from mean annual suicide rates is not a useful tool for identifying months with temperatures that are colder or warmer than the annual average. Therefore, it appears that the seasonality of suicides is due to factors other than temperature.

Direct perfusion measurements of cancellous bone anisotropic permeability.

More extensive characterization of trabecular connectivity and intertrabecular space will be instrumental in understanding disease states and designing engineered bone. This project presents an experimental protocol to define the directional dependence of transport properties as measured from healthy cancellous bone when considered as a biologic, porous medium. In the initial design phases, mature bovine bone was harvested from the femoral neck (n=6 cylinders) and distal condyle (n=4 cubes) regions and used for "proof of concept" experimentation. A power study on those results led to the presented work on 20 cubic samples (mean volume=4.09cm(3)) harvested from a single bovine distal femur. Anisotropic intrinsic permeabilities (k(i)) were quantified along the orthogonal anatomic axes (i=medial-lateral, anterior-posterior, and superior-inferior) from each individual cubic bone sample. Using direct perfusion measurements, permeability was calculated based upon Darcy's Law describing flow through porous media. The maximum mean value was associated with the superior-inferior orientation (4.65x10(-10)m(2)) in comparison with the mean anterior-posterior (4.52x10(-10)m(2)) and medial-lateral (2.33x10(-10)m(2)) direction values. The results demonstrate the anisotropic (p=0.0143) and heterogeneous (p=0.0002) nature of the tissue and encourage the ongoing quantification of parameters within the established poroelastic models.

Compartment syndrome after Bosworth fracture-dislocation of the ankle: a case report.

There are only a few reported cases of compartment syndrome after an ankle fracture, and all have involved the deep posterior compartment. We present a case in which a patient had a Bosworth fracture-dislocation of the ankle, underwent open reduction internal fixation, and subsequently had an anterior compartment syndrome of the leg. Early recognition and prompt treatment are essential to avoid the late sequelae of compartment syndrome.

The Streptomyces venezuelae pikAV gene contains a transcription unit essential for expression of enzymes involved in glycosylation of narbonolide and 10-deoxymethynolide.

In Streptomyces venezuelae, four polyketide synthase (PKS) polypeptides encoded by pikAI-pikAIV are used to generate 10 and 12-membered macrocyclic structures, narbonolide and 10-deoxymethynolide. Sequence analysis suggests these genes are translationally coupled with downstream genes, pikAV (encoding a type II thioesterase), desVIII-desVI (encoding enzymes responsible for production of the final glycosylated products pikromycin, narbomycin, methymycin and neomethymycin) and desR (a resistance gene). Type II thioesterases have been suggested to have an editing function in polyketide biosynthesis and deletion of the corresponding genes often leads to decreased levels of polyketide production. Surprisingly an in-frame deletion of 687 bp of the 843 bp pikAV ORF led to a strain SC1022 that produced normal yields of polyketide products, but only in the aglycone form. Plasmid-based expression of the desVIII-VI and desR in the SC1022 strain completely restored production of glycosylated products, despite the absence of a functional pikAV gene product. Under these conditions the PikAV TEII therefore does not play an important role in polyketide biosynthesis, and its function remains an enigma. These observations also demonstrate that the region of pikAV DNA deleted in strain SC1022 contains a transcription unit essential for expression of the des genes. A sequence alignment of PikAV with members of the highly conserved type II thioesterases revealed a short divergent region at the carboxy terminus, suggesting a region of pikAV that might contain such a transcription unit. DNA containing this region of pikAV was shown to be able to increase plasmid-based expression of both crotonyl CoA reductase gene (ccr) and the erythromycin resistance gene (ermE) in S. venezuelae.

AIDS in Mexican prisons.

PIP: The human rights organization Americas Watch, which toured Mexican prisons, reported in 1991 that all prisoners with HIV infection in the Mexico City area were housed in a single AIDS ward in Santa Marta Prison. In 1991, the 16-bed facility had 15 patients; in 1993, this number had increased by 5. In Mexico City, with 3 prisons holding over 2000 male adults each, there were only 20 known infected prisoners in the AIDS ward at Santa Marta. In 1991, authorities at Matamoros, in the state of Tamaulipas, insisted that none of their inmates had ever been diagnosed as infected with HIV. The prison physician at Reynosa indicated that only 2 inmates since 1985 had ever been diagnosed as infected. In 1992, the prison in Saltillo, in the state of Coahuila, reported that here had yet to be a single positive test for HIV. The prison at Reynosa held 1500 people and only 2 inmates were diagnosed as having AIDS between 1985 and 1991. Prisons at Matamoros and Saltillo held similar numbers but had no experience of infected inmates. A survey of 2 prisons in the state of Tamaulipas indicates that around 12% of the population may use IV drugs, and 9% indicate sharing needles. It is possible for prisoners to die of diseases like pneumonia, associated with AIDS, without the connection to AIDS being diagnosed. Each state, and possibly each prison in Mexico, has its own particular AIDS policies. Santa Marta was the single facility in Mexico City used to house AIDS-infected prisoners, who were segregated. Finally, the prison at Saltillo required all women entering the facility to have a medical examination, including a test for HIV. High-level prison personnel have demonstrated ignorance and fear of AIDS and intolerance of infected prisoners. Mexico must reassess the need to provide adequate medical care to offenders who are sick and dying behind bars.^ieng

Jail suicide and legal redress.

Suicide is the leading cause of death in jails. Especially at risk are pretrial detainees. This paper provides clinicians who serve as consultants to jails with an overview of legal precedent concerning liability for jail suicide on the federal appellate, federal district, and state levels. Liability on the federal level is based upon actions involving deliberate indifference or gross negligence. A table is provided granting a summary view of appellate-level decisions on liability for jail suicide. Liability on the state level involves lesser standards of negligence. The paper concludes with several liability-generating scenarios.

Prostatectomy in the over 80-year-old.

With an ageing population the demand for prostatectomy in the over 80-year-olds is increasing. This study assesses the place of prostatectomy in this age group. All patients over the age of 80 who underwent prostatectomy in a 2-year period were studied retrospectively; 90 such patients underwent 94 operations, 90 of which were TURPs. Serious concomitant disease was found in 64 patients (71%) and 11 (12%) had had a previous prostatectomy at least 1 year before. The mean weight of tissue removed was 24.8 g. In 18 men histology showed malignant change. Two men died from cardiovascular disease immediately after surgery (2.1%); a further 5 patients (7.8%) died within 6 months. Post-operative morbidity was high, with 64 patients (71%) developing complications. These were related to pre-operative urinary tract infections and uraemia. Nevertheless, at 6 weeks 72 patients (80%) were considered to have had a satisfactory result. Prostatectomy in the over 80-year-old has a good long-term outcome. Although the morbidity rate is high, these patients should be considered for operation provided they undergo careful pre-operative assessment.

Tumour markers in prostatic carcinoma. A comparison of prostate-specific antigen with acid phosphatase.

A study was performed on 130 men to compare the level of serum prostate-specific antigen (PSA) in controls, patients with benign prostatic hyperplasia (BPH) and patients with prostatic carcinoma. The results showed that all 30 normal controls below 40 years of age had values less than 10 ng/ml. Of the 40 patients with BPH, all aged over 40 years, 13 (32.5%) had raised levels above 10 ng/ml. In the 60 patients with prostatic carcinoma, all over 40 years, 24 had localised disease (MO) and 36 had metastatic spread (M1), as judged by isotope bone scan. In patients with MO disease, 16 (66.6%) had raised PSA levels compared with 34 (94.5%) of those with M1 disease. The corresponding figures for raised prostatic acid phosphatase (PAP) values were 4% in the MO group and 52.7% in the M1 group. PSA levels reflected neither the histological grade nor the local stage of the tumour and were of no value in estimating tumour burden. PSA was found to be a valuable index in the management of prostatic cancer because of this sensitivity. Stable disease not requiring hormonal manipulation was reflected by unchanging levels of PSA, whereas progressive disease requiring hormonal therapy was reflected by an alteration in the PSA levels corresponding to the patients' response. The same group of progressive disease patients showed only a 50% rise in serum PAP levels, confirming the greater sensitivity of PSA as a measure of prostate cancer. PSA measurements should be included in any further trials on prostatic carcinoma and should be regarded as a standard marker for evaluating response to therapy.

Identification of the poor risk patient with "prostatism" and detrusor failure.

Twenty-five patients with "prostatism" and chronic retention of urine have been followed up for 4 years to determine the natural history of the disorder and results of elective treatment. Twenty-one patients with low pressure during bladder filling maintained normal upper tracts and renal function; they were subdivided by micturition pressure into two groups which differed significantly in terms of both total bladder capacity and variance of capacity. Patients with good voiding pressures had a very satisfactory outcome following surgery, with almost complete relief of symptoms, but patients with poor voiding pressures obtained a poor symptomatic and urodynamic result from repeated surgical procedures. Four patients declined operation and the subsequent course of the disorder is described. Four patients had painless retention associated with high pressure bladder filling, hydronephrosis and uraemia. Operation was successful in reversing these potentially terminal complications. None of the 25 patients developed acute retention. Men with "prostatism" do not constitute a homogeneous population. Identification of specific patient groups enables an accurate prediction of the consequences of both conservative and operative management.

Treatment of bladder carcinoma with tumor-immune pig lymph node cells. Phase I study.

A total of 77 patients with invasive TCC of the urinary bladder each received a single arterial injection of tumor-immune pig lymph node cells (LNC), into the tumor blood supply. The patients were divided into 4 groups: those receiving pig LNC as the only treatment (16 patients); those who received pig LNC on relapse (judged by EUA cystoscopy and biopsy) following radical radiotherapy, 5,500 cGy (34 patients); those who received pig LNC followed after an interval of six weeks by radiotherapy, 4,000 cGy (10 patients); as in Group 3 but with the dose of radiotherapy increased to 5,500 cGy (17 patients). Complete remission was characterized by complete disappearance of the tumor (for a varying time) following treatment. Partial remission was defined as: a reduction in the level of symptoms and a decrease in tumor size on EUA and/or cystoscopy. There were 1 complete and 3 partial remissions among the patients in Group 1, 5 complete and 7 partial in Group 2, 6 complete and 2 partial in Group 3, and 8 complete and 1 partial in Group 4. Of the 20 patients showing complete remission, 7 lived for more than five years after treatment.

Long-term results of optical urethrotomy.

In a 7-year period 137 men with urethral stricture underwent optical urethrotomy. Over 91% were relieved of their stricture symptoms and required no further treatment, including 41 patients in whom the follow-up period exceeded 4 years. The surgical technique is outlined. Strictures with the best prospect of cure were short and single. Optical urethrotomy is confirmed as the treatment of choice in strictures of the male urethra.

Extraurinary manifestations of chronic pyonephrosis.

Twenty-five patients who underwent nephrectomy for chronic pyonephrosis were studied retrospectively. Such patients may present with a wide range of symptoms. Marked haematological and biochemical abnormalities are found, the most striking being a gross elevation of plasma viscosity (or ESR) and a raised alkaline phosphatase. The resulting picture often suggests extrarenal disease, and diagnostic confusion occurred in a number of patients.

"Honeymoon" cystitis: a simple surgical cure.

Post-coital cystitis was treated by an advancement urethroplasty in 41 patients. Twenty-eight patients were either cured or obtained significant relief of symptoms. These encouraging results indicate that a urethroplasty should be considered in suitable cases when conservative methods of treatment have failed, and especially in patients whose urethral meatus lies in an intravaginal position.

Half-body irradiation in the treatment of metastatic prostatic carcinoma.

High dose radiation therapy given as a single fraction to the upper and lower halves of the body gives effective palliation for metastatic solid tumours. This treatment modality appears to be particularly effective in tumours which may have a slow doubling time such as carcinoma of the prostate. Fifty-two patients with metastatic carcinoma of the prostate involving the skeletal system have received half-body irradiation. All had prior treatment with additive hormones or orchiectomy and the majority had received localised irradiation and/or chemotherapy. Significant immediate pain relief was achieved in 42 out of 52 patients (80%). This pain relief was maintained until death in 29 out of 43 patients (67%). Pain relief in responders appears to occur within 24 to 48 h of treatment.

Surgical management of urethral stricture in the male.

Urethral dilatation has long been the standard treatment for patients with urethral stricture. However, in many patients such dilatations may be difficult, painful, or have to be done at frequent intervals. The alternative techniques of direct vision urethrotomy or urethroplasty have been considered in 101 patients over a twelve-year period. Skin inlay urethroplasty in this series showed a significant level of complications and an absolute failure rate of 15 per cent. A prospective study of 39 patients undergoing urethrotomy using the Sachse optical urethrotome has shown that 82 per cent of patients are symptom-free and 13 per cent symptomatically improved at a follow-up ranging from sixteen months to three and one-half years (mean twenty-five months). We believe that urethrotomy using the Sachse optical urethrotome should now be the initial treatment of choice in the management of urethral stricture. Urethral dilatations or urethroplasty should be reserved for those patients who have persisting stricture despite such urethrotomy.

Lipid barrier to water exchange in reptile epidermis.

Extraction of lipids from the shed epidermis of the terrestrial snake Elaphe obsoleta obsoleta increases cutaneous water loss in vitro as much as 15-fold. Partial denaturation of epidermal keratin without lipid extraction increases cutaneous water loss only twofold. Histological observations and thin-layer and gas-liquid chromatography of the lipid extracts indicate a complex mixture of polar and neutral lipids predominantly in the mesos layer of the cornified epidermis. Comparative measurements of cutaneous water loss in other species of snakes and a lizard show that permeabilities differ naturally but are essentially identical after lipid extraction. These findings establish the importance of lipids in the permeability barrier of reptilian skin and suggest that keratin or scale morphology are of nominal importance in limiting water exchange.

A transverse tubular system and neuromuscular junctions in a molluscan unstriated muscle.

The buccal mass retractor muscles of Philine aperta are unusual in possessing a system of transverse tubules in what are in other respects typical unstriated muscle fibres. The tubules are formed from invaginations of the sarcolemma that penetrate up to 9 micron radially into the fibre. There is some indication that the tubules are zoned at certain points along the fibre. Physiologically, the outer membrane of the muscle fibre does not support an action potential, and the fibre contracts by summation of small twitches in response to individual excitatory junction potentials. Neuromuscular junctions occur in shallow grooves along the surface of the fibres. They contain 3 types of vesicles; clear, intermediate and dense-cored. A scheme suggesting how striated muscle may be derived from the unstriated condition is described.